The U.S. Food and Drug Administration granted bb2121, an anti–B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy, breakthrough-therapy designation for previously treated patients with relapsed or refractory multiple myeloma (MM). The decision was based on preliminary data from the ongoing phase I CRB-401 study, from which updated findings will be presented at the 2017 ASH Annual Meeting.
Yi Lin, MD, PhD, assistant professor of medicine and oncology at the Mayo Clinic in Rochester, New York, presented early results from CRB-401 at the 22nd Annual European Hematology Association Congress in June 2017. Eligible patients were required to have undergone at least three prior treatments, including a proteasome inhibitor and an immunomodulatory agent, or were double-refractory with â‰¥50 percent BCMA expression. A total of 21 patients (median age = 58 years; range not provided) were treated in five dose cohorts ranging from 5.0Ã—107 to 120Ã—107 CAR-positive T cells.
Patients underwent leukapheresis and a lymphodepletion conditioning chemotherapy regimen consisting of cyclophosphamide and fludarabine for three days followed by two days of rest before the CAR T-cell infusion. Patients' mononuclear cells were then shipped to a central facility for manufacturing.
Most patients (75%) demonstrated a very good partial response or better, and 27 percent had complete response. The objective response rate across all dose levels was 89 percent (95% CI 65-99). The median time to first response was 31 days, and the median time to best response was 50.5 days (ranges not provided). The duration of response was 134 days and longer (95% CI 7-361).
Fifteen patients (71%) experienced cytokine release syndrome (CRS), two patients had grade 3 CRS that resolved within 24 hours, and four patients had grade 1/2 CRS; four patients received tocilizumab and one grade 1 CRS was treated with steroids. Two patients had pyrexia. No cases of grade 3/4 neurotoxicity were reported.
Investigators hope to eventually enroll 50 heavily pretreated patients with MM from seven sites. The primary endpoint of the trial is the incidence of adverse events and abnormal laboratory test results, which include dose-limiting toxicities.
Source: Celgene press release, November 16, 2017.